Hypoxic-Ischemic Encephalopathy: A Review for the Clinician
Abstract
IMPORTANCE: Hypoxic-ischemic encephalopathy (HIE) occurs in 1 to 8 per 1000 live births in developed countries. Historically, the clinician has had little to offer neonates with HIE other than systemic supportive care. Recently, the neuroprotective therapy of hypothermia has emerged as the standard of care, and other complementary therapies are rapidly transitioning from the basic science to clinical care. OBJECTIVE: To examine the pathophysiology of HIE and the state of the art for the clinical care of neonates with HIE. EVIDENCE REVIEW: We performed a literature review using the PubMed database. Results focused on reviews and articles published from January 1, 2004, through December 31, 2014. Articles published earlier than 2004 were included when appropriate for historical perspective. Our review emphasized evidence-based management practices for the clinician. FINDINGS: A total of 102 articles for critical review were selected based on their relevance to the incidence of HIE, pathophysiology, neuroimaging, placental pathology, biomarkers, current systemic supportive care, hypothermia, and emerging therapies for HIE and were reviewed by both of us. Seventy-five publications were selected for inclusion in this article based on their relevance to these topics. The publications highlight the emergence of serum-based biomarkers, placental pathology, and magnetic resonance imaging as useful tools to predict long-term outcomes. Hypothermia and systemic supportive care form the cornerstone of therapy for HIE. CONCLUSIONS AND RELEVANCE: The pathophysiology of HIE is now better understood, and treatment with hypothermia has become the foundation of therapy. Several neuroprotective agents offer promise when combined with hypothermia and are entering clinical trials.
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Emerging evidence highlights that factors such as hypocapnia, hyperoxia, extreme fluctuations in blood pressure and glucose are associated with worse outcomes in neonates with HIE.
“Emerging evidence highlights that factors such as hypocapnia, hyperoxia, extreme fluctuations in blood pressure and glucose are associated with worse outcomes in this population (1, 4–8).”
From Lab values in neonates with hypoxic ischemic encephalopathy over time during and after therapeutic hypothermia (2026) · cites this paper as [1]
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Self-citation
- Authors
- Douglas-Escobar, M., & Weiss, M. D.
- Affiliations
- Department of Pediatrics, University of California, San Francisco
- University of Florida (US)
- ORCID
- Weiss, Michael D.
- Venue
- JAMA Pediatrics
- Publisher
- American Medical Association (AMA)
- Published
- 2015-04-01
- Volume
- 169
- Issue
- 4
- Pages
- 397
- ISSN
- 1072-4710 (ISSN-L)
- 2168-6203
- OpenAlex
- W2157633141
- Cited by
- 778
- References
- 68
- Citations by year
- 2026: 65 · 2025: 91 · 2024: 108 · 2023: 94 · 2022: 89 · 2021: 98 · 2020: 85 · 2019: 57 · 2018: 36 · 2017: 27 · 2016: 22 · 2015: 6
- FWCI
- 30.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Pediatrics and Adolescent Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal and fetal brain pathology
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Thermal Regulation in Medicine
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Infant Development and Preterm Care
- Keywords
- hypoxic-ischemic encephalopathy, neonatal brain injury, therapeutic hypothermia, neuroprotection, pathophysiology, serum biomarkers, placental pathology, magnetic resonance imaging, neuroimaging, long-term outcome prediction, neuroprotective agents
- MeSH terms
- Combined Modality Therapy, Female, Humans, Hypothermia, Induced, Infant, Newborn, Placenta, Pregnancy, Biomarkers, Neuroprotective Agents, Hypoxia-Ischemia, Brain, Neuroimaging
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